The myelosuppressed patient with cancer may develop pneumonias which are difficult to diagnose. Thus, aggressive diagnostic procedures are warranted. This study utilized a step-wise, orderly method for diagnosing unexplained pulmonary infiltrates utilizing transtracheal aspiration, transtracheal bronchial brushing, fiberoptic bronchoscopy or percutaneous lung biopsies when other methods have failed. Transtracheal aspiration led to diagnosis in about 20-30% of cases. Bronchial brushing yielded diagnostic information in about 30% of cases overall and in nearly 80% of those ultimately proven to have infectious problems. Thirty to 40% of cases are ultimately shown to have noninfectious etiologies such as metastases, interstitial fibrosis or subsegmental collapse. Among the infectious etiologies the diagnosis included a variety of micro-organisms: bacterial, protozoal and fungal. Significant but non-fatal complications occurred and were acceptable risks for the patient population. There was no mortality associated with the procedures, and despite pancytopenia, bleeding was a problem in only 3 patients. This step-wise aggressive diagnostic procedure has proven to be clinically efficacious in 80% of the patients with ultimately documented pneumonias and is now considered standard therapy.